Improved HER2 Tumor Segmentation with Subtype Balancing using Deep Generative Networks

Tumor segmentation in histopathology images is often complicated by its composition of different histological subtypes and class imbalance. Oversampling subtypes with low prevalence features is not a satisfactory solution since it eventually leads to overfitting. We propose to create synthetic images with semantically-conditioned deep generative networks and to combine subtype-balanced synthetic images with the original dataset to achieve better segmentation performance. We show the suitability of Generative Adversarial Networks (GANs) and especially diffusion models to create realistic images based on subtype-conditioning for the use case of HER2-stained histopathology. Additionally, we show the capability of diffusion models to conditionally inpaint HER2 tumor areas with modified subtypes. Combining the original dataset with the same amount of diffusion-generated images increased the tumor Dice score from 0.833 to 0.854 and almost halved the variance between the HER2 subtype recalls. These results create the basis for more reliable automatic HER2 analysis with lower performance variance between individual HER2 subtypes.

Superpixel Pre-Segmentation of HER2 Slides for Efficient Annotation

Supervised deep learning has shown state-of-the-art performance for medical image segmentation across different applications, including histopathology and cancer research; however, the manual annotation of such data is extremely laborious. In this work, we explore the use of superpixel approaches to compute a pre-segmentation of HER2 stained images for breast cancer diagnosis that facilitates faster manual annotation and correction in a second step. Four methods are compared: Standard Simple Linear Iterative Clustering (SLIC) as a baseline, a domain adapted SLIC, and superpixels based on feature embeddings of a pretrained ResNet-50 and a denoising autoencoder. To tackle oversegmentation, we propose to hierarchically merge superpixels, based on their content in the respective feature space. When evaluating the approaches on fully manually annotated images, we observe that the autoencoder-based superpixels achieve a 23% increase in boundary F1 score compared to the baseline SLIC superpixels. Furthermore, the boundary F1 score increases by 73% when hierarchical clustering is applied on the adapted SLIC and the autoencoder-based superpixels. These evaluations show encouraging first results for a pre-segmentation for efficient manual refinement without the need for an initial set of annotated training data.

Fast whole-slide cartography in colon cancer histology using superpixels and CNN classification

Whole-slide-image cartography is the process of automatically detecting and outlining different tissue types in digitized histological specimen. This semantic segmentation provides a basis for many follow-up analyses and can potentially guide subsequent medical decisions. Due to their large size, whole-slide-images typically have to be divided into smaller patches which are then analyzed individually using machine learning-based approaches. Thereby, local dependencies of image regions get lost and since a whole-slide-image comprises many thousands of such patches this process is inherently slow. We propose to subdivide the image into coherent regions prior to classification by grouping visually similar adjacent image pixels into larger segments, i.e. superpixels. Afterwards, only a random subset of patches per superpixel is classified and patch labels are combined into a single superpixel label. The algorithm has been developed and validated on a dataset of 159 hand-annotated whole-slide-images of colon resections and its performance has been compared to a standard patch-based approach. The algorithm shows an average speed-up of 41% on the test data and the overall accuracy is increased from 93.8% to 95.7%. We additionally propose a metric for identifying superpixels with an uncertain classification so they can be excluded from further analysis. Finally, we evaluate two potential medical applications, namely tumor area estimation including tumor invasive margin generation and tumor composition analysis.